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Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 415 records · Page 23Linked to original sources

Altered noradrenergic projection to hypothalamus via baroreflex in spontaneously hypertensive rats.

To determine whether noradrenergic projections to the posterior hypothalamus via baroreflex are altered in the hypertensive state, the extracellular norepinephrine (NE) content of the posterior hypothalamus was measured in both spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) after sinoaortic denervation (SAD) or sham operation. In WKY, blood pressure (BP) and extracellular NE content 24 h after SAD were significantly higher than those of sham-operated rats. Contrarily, SAD did not increase both BP and NE in the posterior hypothalamus of SHR. These results suggest that the noradrenergic pathway via the baroreflex is impaired in SHR. This mechanism may play an important role in the development and maintenance of hypertension in SHR.

Adrenergic Fibers↗

Arrhythmogenic properties of the ventricular myocardium in cardiomyopathic Syrian hamster, BIO 14.6 strain.

STUDY OBJECTIVE: Incidence of spontaneous cardiac arrhythmias and inducibility of ventricular arrhythmias in the cardiomyopathic hamster, BIO 14.6 strain, were examined. DESIGN: A 3 min electrocardiogram (ECG) was recorded weekly to 50 weeks of age. Programmed ventricular stimulation was then performed with single and double ventricular premature stimuli during both sinus rhythm and ventricular pacing, and with brief bursts of ventricular pacing to induce ventricular arrhythmias. EXPERIMENTAL MATERIAL: 19 male cardiomyopathic and 10 age matched normal hamsters from 16 to 50 weeks were used for recording the 3 min ECG; 11 cardiomyopathic and 10 normal hamsters aged 50 to 55 weeks were used for the induction of ventricular arrhythmias. MEASUREMENTS AND MAIN RESULTS: Spontaneous and sporadic ventricular premature contractions were documented in 8.3% of 218 ECGs from the cardiomyopathic hamsters between the ages of 30 and 46 weeks, whereas no ventricular arrhythmia was recorded in normal hamsters throughout the entire follow up period. Non-sustained ventricular tachycardia (NSVT) was induced in 7/11 cardiomyopathic hamsters by single ventricular premature stimulus. Either NSVT or ventricular fibrillation was induced in all cardiomyopathic hamsters with a significantly prolonged intraventricular conduction delay and refractory period. In contrast, neither NSVT nor ventricular fibrillation was induced in normal hamsters. CONCLUSION: This study provides the first evidence of the high arrhythmogenicity of the ventricles in cardiomyopathic hamsters.

Animals↗

[Evaluation of micro particle enzyme immunoassay technique (MEIA)-IMx for the detection of antibody to hepatitis B core antigen].

The new Micro Particle Enzyme Immunoassay technique (MEIA, IMx HBc, Abbott) has been recently introduced for the detection of the antibody to hepatitis B core antigen (anti-HBc). To evaluate the feasibility of using the IMx-HBc, we carried out comparison tests with this method and RIA using various sera. Results obtained were as follows: In the test of 813 sera, 427 (52.3%) were positive by both IMx and RIA, two (0.2%) were positive by RIA only, and the remaining 384 (47.3%) were negative by both methods. A good correlation between IMx and RIA was observed with a coincidence rate of 99.8% and a correlation coefficient of 0.969. Examination of diluted sera using IMx revealed that IMx can be used as efficiently was RIA: high anti-HBc titer was found among HBsAg carriers, but not among non HBsAg carriers. Anti-HBc was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method. These results indicate that the sensitivity of IMx is equivalent to that of RIA, and that it is easier to use than RIA.

Adult↗

[Evaluation of micro particle enzyme immunoassay technique (MEIA)-IMx for the detection of IgM class antibody to hepatitis B core antigen].

The new Micro Particle Enzyme Immunoassay technique (MEIA, IMx HBc-M, Abbott) had been recently introduced for the detection of IgM class antibody to hepatitis B core antigen (IgM anti-HBc). To evaluate the feasibility of using the IMx HBc-M, we carried out comparison tests between this method. RIA and EIA using sera from acute hepatitis B and type B chronic liver disease. Results obtained were as follows: In the test of 98 sera from acute hepatitis B patients, 92 (93.9%) were positive for IgM anti-HBc by IMx HBc-M, 96 (98.0%) by RIA and 82 (83.7%) by EIA. The four sera which were positive by RIA, but not by IMx were ones obtained from 5 to 12 month after onset. In the test of 267 sera from B type chronic liver disease patients, 93 (34.8%) were positive by IMx HBc-M, 109 (40.8%) by RIA and 23 (8.6%) by EIA. There was a difference in the positive rate between IMx HBc-M and RIA among type B chronic liver disease: the positive rate was higher in RIA than in IMx HBc-M among type B active chronic hepatitis, but only a little higher in IMx HBc-M than RIA among hepatocellular carcinoma. IgM anti-HBc titer was significantly higher in acute hepatitis type B than in chronic liver disease, and was so even in the phase of HBsAg negative in acute hepatitis. IgM anti-HBc was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[An epidemiologic study of anti-HTLV-I (antibody to human T cell lymphotropic virus type I) by category of disease in the Kushima district of Miyazaki prefecture].

HTLV-I seroprevalence in the southern part of Miyazaki prefecture was reported to be high in many seroepidemiological surveys. In order to determine the distribution of antibody to Human T-cell lymphotropic virus type I (anti-HTLV-I) in the Kushima district of Miyazaki prefecture and evaluate the relation between the HLTV-I carrier and disease, determination of anti-HTLV-I status of patients in a hospital in Kushima City, Miyazaki prefecture was carried out from March to July, 1985. Sera from 542 patients was tested for presence of anti-HTLV-I by particle agglutination (PA) and indirect immunofluorescence (IF). Results obtained area as follows 1) Overall prevalence of anti-HTLV-I was 31.2 per cent (169 of 542 individuals). It increased gradually with age and elevated remarkably in the 60-69 age group, showing the highest rate of 39.6 per cent. 2) Prevalence of anti-HTLV-I was 28.6 per cent (65 of 227) in males and 33.0 per cent (104 of 315) in females. A significant difference by sex was not recognized. 3) No significant difference was found in the geographical distribution of anti-HTLV-I, but prevalence in the Toi area was relatively low. 4) Anti-HTLV-I was prevalent in the patients with tuberculosis (46.2 per cent), most of whom had a history of blood transfusion. In this study, the relation between HTLV-I carriers and diseases was not analysed. 5) Seroprevalence of anti-HTLV-I in the patients who had had blood transfusions was significantly higher than that of those who had not had blood transfusions (p less than 0.01).

Adolescent↗

[Evaluation of micro enzyme immunoassay technique (MEIA) for the demonstration of hepatitis B surface antigen].

The new Micro Particle Enzyme Immunoassay technique (MEIA, IMx HBsAg, Abbott) has been recently introduced for the detection of the presence of hepatitis B surface antigen (HBsAg). The present trial was carried out to determine the feasibility of using the IMx HBsAg with sera and plasma, and for comparison with RIA (Ausria II, Abbott) and RPHA (Reversecell, Megroken). Results obtained were as follows: In the test of 622 sera from inhabitants in Okinawa, 455 (73.1%) using IMx were positive for HBsAg, 454 (73.0%) with RIA, and 330 (53.0%) with RPHA. Five of the 179 tests using plasma from hemodialysis patients were positive for HBsAg with both IMx and RIA. One of these 5 was negative for HBsAg with RPHA. The difference of HBsAg positive rates between IMx and both RIA and RPHA increased with advancing age. Twenty four individuals were followed up from three to ten years and had had it confirmed that HBsAg had become negative in their sera, HBsAg was still positive from one to four years in both IMx and RIA after HBsAg became negative in RPHA. It was noted that HBsAg was assayed within one hour by IMx, and that the procedure was simple because of the autoanalyser equipped for this method. The results indicate that the sensitivity of IMx might be equal to that of RIA more than that of RPHA, and easier to measure than either of the others.

Adolescent↗

[A case of tsutsugamushi disease in the urban area of Komatsu City].

Most of patients with tsutsugamushi disease are diagnosed by their clinical histories suggesting the opportunities of Rickettsia infection in a rural region. We reported a 76-year-old female patient, who was considered to be infected in her house in the urban area of Komatsu City. She has shown typical clinical manifestations of tsutsugamushi disease, and was remitted successfully by oral administration of minocycline. Although specific antibodies to Rickettsia tsutsugamushi could not be detected in her serum by the complement fixation (CF) method during her clinical course, their significant elevation was confirmed by the indirect immunofluorescence (IF) method.

Aged↗

Local skin response in mice induced by a single intradermal injection of bacterial lipopolysaccharide and lipid A.

Dermal inflammation and hemorrhagic necrosis induced by bacterial lipopolysaccharide (LPS) and lipid A were studied in mice. In ddY mice, a single intradermal injection of Salmonella typhimurium S-form LPS and lipid A into the abdominal dermis elicited an edematous change due to an increase in local vascular permeability 12 h postinjection, followed by hemorrhagic necrosis from 24 to 72 h. This skin reaction was also induced in a dose-dependent manner by S-form LPS, R-mutant LPS, and lipid A of S. typhimurium and Escherichia coli, but not by polysaccharide from Salmonella S-form LPS. The dermal inflammation-inducing activities of LPS and lipid A were roughly in the following order (from highest to lowest): Re-form LPS, Rc-form LPS and lipid A, Ra-form LPS, and S-form LPS. These results suggest that the lipid A portion of the LPS molecule is responsible for the skin reaction. In C3H/HeN mice, Re-form LPS and lipid A induced the same intensity of skin reaction as that in ddY mice. In C3H/HeJ mice, which have a low response to LPS, Re-LPS and lipid A did not induce any hemorrhagic response but showed a distinct edematous change. Although hemorrhagic necrosis and edematous changes could be explained by quantitative differences in skin lesions, the other possible explanation is that hemorrhagic necrosis and the increase in local vascular permeability are induced by different mechanisms, only one of which depends on the regulation of the lps gene.

Animals↗

Effects of immunization against VIP on neurotransmission in cat trachea.

To examine the possible role of vasoactive intestinal polypeptide (VIP) in excitatory and inhibitory neurotransmission and physiological function of coexistence VIP and acetylcholine at vagus nerve terminals in the cat trachea, we immunized five cats each against conjugate of VIP-bovine serum albumin (BSA) and BSA, respectively. A booster injection of VIP-BSA given 3 wk after the primary one elevated antibodies against VIP, as detected by enzyme-linked immunosorbent assay, but not in the control cats identically injected with BSA. After immunization, in vitro, summation phenomena observed in the amplitude of contractions and excitatory junction potentials of the trachea evoked by repetitive field stimulation were markedly enhanced, whereas the amplitude of phasic relaxation evoked by repetitive field stimulation in the presence of serotonin, atropine, and guanethidine was markedly reduced. In contrast, in vivo, the change in pulmonary resistance evoked by vagal stimulation was not affected in the immunized cats. We conclude that antibodies against neurotransmitter VIP are a potential modulatory factor in excitatory and inhibitory neurotransmission in airway smooth muscle at tissue or cellular levels. The lack of correlation between in vivo and in vitro conditions was discussed in relation to VIP autoantibodies in normal and asthmatic humans.

Animals↗

Influence of sympathetic nerve activity on ventricular arrhythmogenicity in the dog with chronic hypokalemia.

To examine the influence of sympathetic nerve activity on ventricular arrhythmogenicity in the dog with chronic hypokalemia, an electrophysiologic study was performed before and after bilateral stellectomy (BS) in 10 dogs with chronic hypokalemia (2.8 +/- 0.1 mEq/L), which was created by feeding a low-potassium diet and by administering furosemide over a four-week period, and the results were compared with those obtained from 10 dogs with normokalemia (4.7 +/- 0.3 mEq/L) from being fed an ordinary diet over a four-week period. Before BS the incidence of electrically induced ventricular arrhythmias was higher in the hypokalemic than in the normokalemic dogs. After BS it was decreased considerably in the hypokalemic but not in the normokalemic dogs. Heterogeneity of effective refractory period (delta ERP), which was determined as the difference between the longest and shortest effective refractory periods in three sites of the right and left ventricles, was greater in the hypokalemic than in the normokalemic dogs before BS. The delta ERP decreased slightly in the two groups both before and after BS. There was, however, no significant difference in delta ERP in the two groups both before and after BS. Ventricular fibrillation threshold (VFT) was significantly lower in the hypokalemic dogs than in the normokalemic dogs before BS (p less than 0.005). VFT was elevated in the two groups after BS. Percent increase in VFT after BS was significantly greater in the hypokalemic than in the normokalemic dogs. In conclusion, sympathetic nerve activity may play an important role in the increase in ventricular arrhythmogenicity in the presence of chronic hypokalemia.

Animals↗

Synthesis of fluorine and iodine analogues of clorgyline and selective inhibition of monoamine oxidase A.

A series of fluorine and iodine analogues of clorgyline was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase A (MAO-A). Among them, N-[3-(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2-propynylami ne (3d), N-[3-(4-chloro-2-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3f) and N-[3-(2-chloro-4-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3g) were found to have high inhibitory potency and selectivity toward MAO-A comparable to those of clorgyline itself. Thus, they were considered for advanced development as radiofluorinated and radioiodinated ligands that may be useful for functional MAO-A studies in the living brain with positron emission tomography and single photon emission computer tomography.

Animals↗

Inhibition of endothelin (ET)-1-and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody.

We produced a monoclonal antibody to endothelin (ET)-1, tested cross-reactivities with the related peptides by enzyme immunoassay, and investigated the effects of the antibody on ET-1- or ET-2-induced vasoconstriction of rat isolated thoracic aorta. The antibody recognized ET-1, ET-2 and ET-3, and the immunoreactive site proved to be the N-terminal region but not the C-terminal region of ET-1. Moreover, at an approximate molar-equivalent concentration, the antibody absorbed ET-1 and ET-2, and significantly inhibited ET-1- and ET-2-induced vasoconstriction notwithstanding the presence of the endothelin receptor.

Animals↗

Preparation and biological activity of 2-[4-(thiazol-2-yl)phenyl]propionic acid derivatives inhibiting cyclooxygenase.

A series of 2-[4-(thiazol-2-yl)phenyl]propionic acids substituted at various positions were prepared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)malonates with alpha-bromoaldehyde diethyl acetals or alpha-haloketones followed by hydrolysis of esters. The inhibition of prostaglandin H synthetase (cyclooxygenase) was assayed by use of an enzyme preparation from guinea pig polymorphonuclear leukocytes. Examination of the structure-activity relationship of these compounds indicated that the substitution pattern with halogens at position 3 (R1) of the benzene ring and a methyl group in position 4 (R2) and/or 5 (R3) of the thiazole ring were favorable for inhibitory activity. The compounds bearing bulky alkyl or polar functional groups at the R2 position were weak inhibitors. The potent inhibitors of cyclooxygenase were tested for their ability to reduce carrageenin-induced inflammation of rat paws. These derivatives had strong anti-inflammatory activity based on their strong inhibition of cyclooxygenase, with some exceptions, including those with a thiomethyl group at R1.

Animals↗

Syntheses and biological activities of endothelin-1 analogs.

Endothelin-1 analogs replaced by various amino acids at position 21, namely [X21]-ET-1, were synthesized, and their agonistic vasoconstrictor activity on rat thoracic aortic strips and receptor binding activity on rat brain membrane fraction were examined to elucidate their structure-activity relationship. The vasoconstrictor activities of [Tyr21]- and [Phe21]-ET-1 were one order of magnitude smaller than that of ET-1, and those of [His21]-, [Gly21]-, [Ser21]-, [Ala21]- and [Lys21]-ET-1 were more than two orders of magnitude smaller than that of ET-1. On the other hand, the replacements by Ile, Glu, Gln and Pro resulted in distinguished losses of the vasoconstrictor activities. In addition, preincubation with these analogs did not blunt ET-1-induced vasoconstriction and showed no antagonistic activity. The binding inhibitory activities of these analogs against 125I-ET-1 were approximately conformable to the vasoconstrictor activities with only a slight exception. These findings demonstrate that the phenyl group at position 21 is important for both the vasoconstrictor activity and the receptor binding activity.

Animals↗

Synthesis of [125I]iodoclorgyline, a selective monoamine oxidase A inhibitor, and its biodistribution in mice.

A new radioiodinated monoamine oxidase A (MAO-A) specific inhibitor, [125I]iodoclorgyline, was synthesized from its tin precursor by iododestannylation reaction using sodium [125I]iodide and hydrogen peroxide with high yield and site specificity. The product possessed a high radiochemical purity as well as high specific activity. The method can be readily applicable for labeling with 123I, a very suitable radioisotope for in vivo imaging with single photon emission computer tomography (SPECT). Biodistribution studies of the [125I]iodoclorgyline in mice showed high initial uptake in the brain, and brain radioactivity reached a constant level at 60 min after intravenous injection. The results suggested that [125I]iodoclorgyline might have potential as a radiopharmaceutical for MAO-A studies in the brain with SPECT.

Animals↗

Enhanced norepinephrine release in hypothalamus from locus coeruleus in SHR.

The hypothesis that a functional projection from the locus coeruleus (LC) to the posterior hypothalamus contributes to the development of hypertension in SHR, was tested by measuring norepinephrine (NE) in the posterior hypothalamus by brain dialysis after injections of L-glutamate (L-glu) into LC. L-glu elicited a prolonged elevation of blood pressure in both SHR and WKY. Pressor effects were significantly larger in SHR than in WKY. Extracellular NE in the posterior hypothalamus increased after LC stimulation; NE release was significantly higher in SHR than in WKY. Injections of 6-hydroxydopamine (6-OHDA) into posterior hypothalamus lowered the resting blood pressure and attenuated the pressor responses to L-glu injections into the LC in SHR. These findings suggest that the LC projects functionally to the posterior hypothalamus and that the projection can contribute to the development of hypertension in SHR.

Animals↗

Effects of sympathetic and parasympathetic stimulation on the induction of atrial flutter in dogs with aseptic pericarditis.

To study the effects of sympathetic stimulation (SS) and vagal stimulation (VS) on the induction of atrial flutter (AF) and its cycle length, aseptic pericarditis was produced surgically in 17 adult mongrel dogs. Programmed atrial stimulation was used to induce AF and to determine the effective refractory periods (ERP) and maximum conduction delay (maxCD) of the atrium. These tests were performed before and during stimulation of the right cervical vagus nerve and the right stellate ganglion. Results showed: (1) AF could be induced in animals with short ERP and large maxCD before SS; (2) ERP was significantly shortened, maxCD was significantly increased by VS; (3) During SS, ERP was slightly shortened, but there were no changes in maxCD and the induction rate of AF; (4) The cycle length of AF was shortened by SS, however, the cycle length of AF was shortened more notably by VS than by SS. From these findings, a shortening of the ERP and an increase in maxCD appear to be related to an increased AF induction rate by VS.

Animals↗